2024-03-29T12:17:38Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/129462024-01-23T10:05:24Zcom_20.500.12105_2145com_20.500.12105_2051com_20.500.12105_2144com_20.500.12105_2109com_20.500.12105_2052col_20.500.12105_2146col_20.500.12105_2110
Repisalud
author
Prieto, Ignacio
author
Zambrano, Alberto
author
Laso, Javier
author
Aranda, Ana
author
Samper, Enrique
author
Monsalve, María
funder
Ministerio de Economía, Industria y Competitividad (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Unión Europea. Comisión Europea. H2020
funder
Instituto de Salud Carlos III
2021-05-12T12:25:15Z
2021-05-12T12:25:15Z
2019
Free Radic Biol Med. 2019 Jul;138:23-32.
http://hdl.handle.net/20.500.12105/12946
31029787
10.1016/j.freeradbiomed.2019.04.015
1873-4596
Free Radical Biology & Medicine
Oxidative stress is known to induce early replicative senescence. Senescence has been proposed to work as a barrier to immortalization and tumor development. Here, we aimed to evaluate the impact of the loss of peroxisome proliferator activated receptor γ co-activator 1α (PGC-1α), a master regulator of oxidative metabolism and mitochondrial reactive oxygen species (ROS) generation, on replicative senescence and immortalization in mouse embryonic fibroblasts (MEFs).
We found that primary MEFs lacking PGC-1α showed higher levels of ROS than wild-type MEFs at all cell passages tested. The elevated production of ROS was associated with higher levels of oxidative DNA damage and the increased formation of DNA double-strand breaks. Evaluation of the induction of DNA repair systems in response to γ-radiation indicated that the loss of PGC-1α also resulted in a small but significant reduction in their activity. DNA damage induced the early activation of senescence markers, including an increase in the number of β-galactosidase-positive cells, the induction of p53 phosphorylation, and the increase in p16 and p19 protein. These changes were, however, not sufficient to reduce proliferation rates of PGC-1α-deficient MEFs at any cell passage tested. Moreover, PGC-1α-deficient cells escaped replicative senescence.
PGC-1α plays an important role in the control of cellular senescence and immortalization.
eng
Immortalization
Mitochondria
Oxidative stress
PGC-1α
Senescence
Early induction of senescence and immortalization in PGC-1α-deficient mouse embryonic fibroblasts
journal article
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